scholarly journals When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

1999 ◽  
Vol 340 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Marco BAGNATI ◽  
Cristina PERUGINI ◽  
Cristiana CAU ◽  
Roberta BORDONE ◽  
Emanuele ALBANO ◽  
...  
Keyword(s):  
Uric Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxides ◽  
Water Soluble ◽  
Ldl Oxidation ◽  
Lag Phase ◽  
Lipid Hydroperoxides ◽  
Low Density ◽  
Oxidant Effect

The inclusion of uric acid in the incubation medium during copper-induced low-density lipoprotein (LDL) oxidation exerted either an antioxidant or pro-oxidant effect. The pro-oxidant effect, as mirrored by an enhanced formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances and increase in negative charge, occurred when uric acid was added late during the inhibitory or lag phase and during the subsequent extensive propagation phase of copper-stimulated LDL oxidation. The pro-oxidant effect of uric acid was specific for copper-induced LDL oxidation and required the presence of copper as either Cu(I) or Cu(II). In addition, it became much more evident when the copper to LDL molar ratio was below a threshold value of approx. 50. In native LDL, the shift between the antioxidant and the pro-oxidant activities was related to the availability of lipid hydroperoxides formed during the early phases of copper-promoted LDL oxidation. The artificial enrichment of isolated LDL with α-tocopherol delayed the onset of the pro-oxidant activity of uric acid and also decreased the rate of stimulated lipid peroxidation. However, previous depletion of α-tocopherol was not a prerequisite for unmasking the pro-oxidant activity of uric acid, since this became apparent even when α-tocopherol was still present in significant amounts (more than 50% of the original values) in LDL. These results suggest, irrespective of the levels of endogenous α-tocopherol, that uric acid may enhance LDL oxidation by reducing Cu(II) to Cu(I), thus making more Cu(I) available for subsequent radical decomposition of lipid peroxides and propagation reactions.

Heme and lipid peroxides in hemoglobin-modified low-density lipoprotein mediate cell survival and adaptation to oxidative stress

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1732-1739 ◽  
Author(s):  
Liana Asatryan ◽  
Ouliana Ziouzenkova ◽  
Roger Duncan ◽  
Alex Sevanian
Keyword(s):  
Oxidative Stress ◽  
Cell Survival ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxides ◽  
Ldl Oxidation ◽  
Lipid Hydroperoxides ◽  
Low Density ◽  
Atherosclerotic Lesions ◽  
Ldl Particles

AbstractLow-density lipoprotein (LDL) oxidation mediated by a variety of catalysts in atherosclerotic lesions plays a crucial role in the genesis and evolution of atherosclerotic plaques. In this study we focused on oxidative properties of hemoglobin (Hb)–modified LDL because Hb is present in atherosclerotic lesions. Under low oxygen tensions Hb was previously found to modify apolipoprotein B100 with covalent binding of Hb fragments and formation of electronegative LDL particles (LDL–). Here we show that HbLDL is highly susceptible to oxidation, but is not cytotoxic to vascular cells, as was found for LDL– isolated from human plasma. HbLDL and LDL– have similar levels of oxidized lipid products and low uptake rates; however, the virtual absence of HbLDL-induced toxicity depends on a marked adaptive oxidative stress response. This was evidenced by a time- and dose-dependent induction of heme oxygenase (HO-1). Cell survival was significantly decreased in the presence of HO-1 inhibitor, tin protoporphyrin (SnPPIX). HO-1 induction by HbLDL increased resistance of cells to toxic doses of hemin or t-BuOOH. The high sensitivity to oxidation and HO-1 induction was largely dependent on lipid hydroperoxides and heme associated with HbLDL. Reduction of pre-existing lipid peroxides using ebselen delayed HbLDL kinetics and inhibited HO-1 induction. Moreover, heme inactivation or its degradation inhibited HO-1 induction and provided an additive inhibitory effect to ebselen. We conclude that Hb-catalyzed reactions may modulate vascular cell survival and oxidative stress adaptation due to the presence of peroxides and heme, thus providing a possible mechanism for the evolution of atherosclerotic and hemorrhagic lesions.

scholarly journals When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

1999 ◽  
Vol 340 (1) ◽  
pp. 143 ◽  
Author(s):  
Marco BAGNATI ◽  
Cristina PERUGINI ◽  
Cristiana CAU ◽  
Roberta BORDONE ◽  
Emanuele ALBANO ◽  
...  
Keyword(s):  
Uric Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Water Soluble ◽  
Low Density ◽  
Lipoprotein Oxidation ◽  
Low Density Lipoprotein Oxidation

scholarly journals The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation

1993 ◽  
Vol 294 (3) ◽  
pp. 829-834 ◽  
Author(s):  
M I Mackness ◽  
C Abbott ◽  
S Arrol ◽  
P N Durrington
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Antioxidant Vitamins ◽  
Ldl Oxidation ◽  
Low Density ◽  
Conjugated Diene ◽  
Peroxide Formation

1. The oxidation of low-density lipoprotein (LDL) is believed to play a central role in atherogenesis. We have compared the effect of antioxidant vitamins and high-density lipoprotein (HDL) on the Cu(2+)-catalysed oxidation of LDL. 2. Antioxidant vitamin supplementation significantly reduced conjugated diene formation but did not affect the formation of lipid peroxides. 3. Conversely, HDL did not affect conjugated diene formation but inhibited the formation of lipid peroxides by up to 90%. 4. The inhibition by HDL of lipid peroxide formation in oxidized LDL was dependent on the concentration of HDL and was not due to HDL chelating Cu2+. 5. Large interindividual variations in the inhibition of lipid peroxide formation by autologous HDL were evident, which were related to the rate of lipid peroxide generation in the LDL. 6. We conclude that HDL is a powerful antioxidant or more probably inhibitor of LDL oxidation in vitro and may play an important role in vivo in preventing atherosclerosis by inhibiting LDL oxidation in the artery wall.

scholarly journals Low-density lipoprotein is the major carrier of lipid hydroperoxides in plasma. Relevance to determination of total plasma lipid hydroperoxide concentrations

1996 ◽  
Vol 313 (3) ◽  
pp. 781-786 ◽  
Author(s):  
Jaffar NOUROOZ-ZADEH ◽  
Jarad TAJADDINI-SARMADI ◽  
K. L. Eddie LING ◽  
Simon P. WOLFF
Keyword(s):  
Total Lipid ◽  
Xylenol Orange ◽  
Low Density Lipoprotein ◽  
Lipid Hydroperoxide ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Lipid Hydroperoxides ◽  
Very Low Density Lipoprotein ◽  
Low Density

High-density lipoprotein (HDL) has been proposed as the principal carrier of hydroperoxides in plasma, based upon data gathered with an HPLC-chemiluminescence technique. To test this hypothesis we have measured total lipid hydroperoxides in native plasma using the ferrous oxidation in Xylenol Orange (FOX) assay and then fractionated plasma into very-low-density lipoprotein, low-density lipoprotein (LDL) and HDL fractions. Hydroperoxides were found to accumulate principally (more than 65%) in LDL, as judged by hydroperoxide content per amount of protein or cholesterol, or expressed as a proportion of total hydroperoxide in plasma. Plasma was also incubated at 37 °C in the presence and absence of 2,2´-azo-bis-(2-amidinopropane) hydrochloride (AAPH), an azo-initiator of lipid peroxidation. The majority of hydroperoxides generated in plasma were recovered in the LDL fraction. Furthermore, when isolated lipoproteins were subject to oxidation initiated by AAPH, very-low-density lipoprotein and LDL showed the greatest propensity for hydroperoxide accumulation, whereas HDL seemed relatively resistant. Estimates for plasma and LDL peroxidation based upon techniques which measure total lipid hydroperoxides suggest that levels of hydroperoxides in plasma and LDL are far higher than that those estimates generated by ostensibly more selective techniques. Higher levels of hydroperoxides in LDL than those reported by HPLC-chemiluminescence also seem in greater accordance with other available data concerning LDL oxidation.

scholarly journals The effects of ascorbate and dehydroascorbate on the oxidation of low-density lipoprotein

1996 ◽  
Vol 320 (2) ◽  
pp. 373-381 ◽  
Author(s):  
Suzanne E. STAIT ◽  
David S. LEAKE
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Conjugated Dienes ◽  
Ldl Oxidation ◽  
Lag Phase ◽  
Prolonged Storage ◽  
Low Density ◽  
Dependent Manner ◽  
Conjugated Diene

Ascorbate at concentrations of 60–100 µM inhibits the modification of freshly prepared low-density lipoprotein (LDL) by macrophages. With ‘moderately oxidized’ LDL (produced by prolonged storage in a refrigerator), however, ascorbate does not inhibit LDL modification by macrophages and actually modifies the LDL itself in the absence of macrophages [Stait and Leake (1994) FEBS Lett. 341, 263–267]. We have now shown that dehydroascorbate can modify both ‘fresh’ LDL and moderately oxidized LDL in a dose-dependent manner to increase its uptake by macrophages. The modification of moderately oxidized LDL by ascorbate and dehydroascorbate or of ‘fresh’ LDL by dehydroascorbate is dependent on the presence of iron or copper. In ‘fresh’ LDL, ascorbate inhibited conjugated-diene formation by copper. In moderately oxidized LDL, the number of conjugated dienes present was decreased rapidly in the presence of copper and ascorbate. Dehydroascorbate decreased the lag phase and increased the rate of copper-induced conjugated-diene formation in ‘fresh’ LDL (although in some experiments it inhibited the formation of conjugated dienes). The ascorbate-modified moderately oxidized LDL was taken up by macrophages by their scavenger receptors, as the uptake was inhibited by polyinosinic acid or fucoidan. Ascorbate and dehydroascorbate therefore have the potential to increase LDL oxidation under certain conditions, but whether or not they do so in vivo is unknown.

scholarly journals Both Hypothyroidism and Hyperthyroidism Enhance Low Density Lipoprotein Oxidation*

1997 ◽  
Vol 82 (10) ◽  
pp. 3421-3424 ◽  
Author(s):  
Vidya Sundaram ◽  
Atef N. Hanna ◽  
Lata Koneru ◽  
H. A. I. Newman ◽  
James M. Falko
Keyword(s):  
Low Density Lipoprotein ◽  
Disease Process ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Lag Phase ◽  
Low Density ◽  
Thyroid Function Tests ◽  
Increased Risk ◽  
Dose Dependent Fashion

Abstract Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that l-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean ± sem hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 ± 0.0.65 and 14 ± 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 ± 0.55 h, and that during the euthyroid phase was 12 ± 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.

scholarly journals Reductions of copper ion-mediated low-density lipoprotein (LDL) oxidations of trypsin inhibitors, the sweet potato root major proteins, and LDL binding capacities

2020 ◽  
Vol 61 (1) ◽  
Author(s):  
Yeh-Lin Lu ◽  
Chia-Jung Lee ◽  
Shyr-Yi Lin ◽  
Wen-Chi Hou
Keyword(s):  
Sweet Potato ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Trypsin Inhibitors ◽  
Water Soluble ◽  
Affinity Column ◽  
Low Density ◽  
Native Page

Abstract Background The root major proteins of sweet potato trypsin inhibitors (SPTIs) or named sporamin, estimated for 60 to 80% water-soluble proteins, exhibited many biological activities. The human low-density lipoprotein (LDL) showed to form in vivo complex with endogenous oxidized alpha-1-antitrypsin. Little is known concerning the interactions between SPTIs and LDL in vitro. Results The thiobarbituric-acid-reactive-substance (TBARS) assays were used to monitor 0.1 mM Cu2+-mediated low-density lipoprotein (LDL) oxidations during 24-h reactions with or without SPTIs additions. The protein stains in native PAGE gels were used to identify the bindings between native or reduced forms of SPTIs or soybean TIs and LDL, or oxidized LDL (oxLDL). It was found that the SPTIs additions showed to reduce LDL oxidations in the first 6-h and then gradually decreased the capacities of anti-LDL oxidations. The protein stains in native PAGE gels showed more intense LDL bands in the presence of SPTIs, and 0.5-h and 1-h reached the highest one. The SPTIs also bound to the oxLDL, and low pH condition (pH 2.0) might break the interactions revealed by HPLC. The LDL or oxLDL adsorbed onto self-prepared SPTIs-affinity column and some components were eluted by 0.2 M KCl (pH 2.0). The native or reduced SPTIs or soybean TIs showed different binding capacities toward LDL and oxLDL in vitro. Conclusion The SPTIs might be useful in developing functional foods as antioxidant and nutrient supplements, and the physiological roles of SPTIs-LDL and SPTIs-oxLDL complex in vivo will investigate further using animal models.

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